Effect of increasing dose level of a novel consensus bacterial 6-phytase variant on phytate degradation in broilers fed diets containing varied phytate levels.

1. The effect of increasing the dose level of a novel consensus bacterial 6-phytase variant on apparent ileal digestibility (AID) of phosphorus (P), phytic acid (inositol hexa-phosphate, IP6) and ileal IP6 degradation profile was studied in diets containing varying phytate-P (PP) levels.2. Ross 308, one-day-old males (n = 1,800) were allocated to cages (20 birds/cage, six cages/treatment) in a completely randomised design employing a 3 × 5 factorial arrangement (three PP levels: 2.45 (low) 2.95 (medium) and 3.45 g/kg (high); five dose levels of phytase (PhyG): 0, 500, 1,000, 2,000 and 4,000 FTU/kg). Phased diets were based on wheat, corn, soybean meal, rapeseed meal and rice bran (d 0 to 10; 2.60 g/kg digestible P, 7.6 g/kg calcium (Ca); d 11 to 21; 2.10 g/kg digestible P, 6.4 g/kg Ca). Ileal digesta was collected on d 21 for determination of P, IP6 and IP-esters content. Data were analysed by factorial ANOVA; means separation was achieved using Tukey's HSD test.3. Increasing PP reduced AID of IP6 and sum of IP3-6 (%) (P < 0.05) but absolute P-release (g/kg diet) above NC was increased (P < 0.05) at high vs. low PP. Increasing phytase dose exponentially increased (P < 0.001) AID IP6, sum of IP3-6 (%) and digestible IP3-6-P g/kg diet (P < 0.001). AID P was increased but there was an interaction with PP level (P < 0.001). Ileal accumulation of IP5-3-P was universally low with PhyG at ≥1,000 FTU/kg (<0.06 g/100 g DM). At 2,000 and 4,000 FTU/kg, AID IP6 was 97.2, 92.7, 92.6% and 100, 97.2, 97.1%, respectively, at low, medium and high PP. At 2,000 FTU/kg, phytate-P release estimated as the increase (above NC) in ileal digestible sum of IP3-6-P in the diet was 2.26, 2.59 and 3.10 g/kg in low, medium and high PP, respectively.4. The data demonstrated that the novel phytase was effective in breaking down phytate to low IP-esters in diets with varied PP content but the optimal dose level for maximising P-release may differ in diets with varying PP content.

Temporal Changes in Photoreducible Mercury, Photoreduction Rates, and the Role of Dissolved Organic Matter in Freshwater Lakes.

Total photoreducible mercury [Hg(II)RED] and photoreduction rates in the surface waters of four lakes in Kejimkujik National Park, Nova Scotia were measured monthly over a summer. The percent of THg that was photoreducible [%Hg(II)RED] decreased significantly in two of the four lakes from early to late summer: North Cranberry (maximum 42% to minimum 14%) and Big Dam East (maximum 51% to minimum 6%). Hg(II)RED was found to have a linear relationship with THg for all combined site data. THg and Hg(II)RED were found to have positive linear relationships with DOC concentrations (R2 = 0.97; n = 36; p < 0.01 and R2 = 0.75; n = 36; p < 0.01, respectively). A smaller proportion of THg was found to be photoreducible with increasing DOC concentration.

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region.

OBJECTIVES: Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4-IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria. MATERIALS AND METHODS: Medical records of all patients diagnosed with a demyelinating disorder in the region from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met. Patients with core symptoms were invited to provide a blood sample for AQP4-IgG analysis with an enzyme-linked immunosorbent assay and a cell-based indirect immunofluorescence assay. RESULTS: In 191 patients with core symptoms, one met the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015 NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively. CONCLUSION: NMO/NMOSD is a rare disease in the Central Denmark Region, with a considerably lower incidence rate than previously estimated in a neighbouring region.

Accuracy of food photographs for quantifying food servings in a lunch meal setting among Danish children and adults.

BACKGROUND: Visual aids, such as food photographs, are widely used in estimating food quantities in dietary surveys. The present study aimed to assess how accurately Danish adults and children can estimate food portion sizes using 37 series of photographs illustrating four to six different portion sizes under real-life conditions; determine whether adults were more accurate than children; and estimate the error caused by using portion size photographs to estimate weights of foods consumed in macronutrient calculation. METHODS: Six hundred and twenty-two adults and 109 children were recruited in three workplace canteens and in two schools, respectively, to estimate their lunchtime portions based on photographs. Participants were instructed to keep the foods separated on their plate when taking lunch. Participants thereafter estimated their own portions by looking at the relevant series of photographs. The actual food portions were then weighed. RESULTS: The proportion of correct estimations was 42% overall (range 19-77%). The mean difference (%) between estimated and actual weight was 17% (range 1-111%). Small portion size photographs were more often used correctly compared to larger portion photographs. Children had as many correct estimations as adults, although they overestimated portions more. Participants using fractions of (or more than) one photograph to estimate the portion of a food had significantly larger errors. When calculating the macronutrient content of a weekly menu using the estimated portion sizes, protein had the largest error (29%). CONCLUSIONS: When used in a real-life situation, the portion size photographs validated in the present study showed a certain inaccuracy compared to the actual weights.

Human endogenous retroviruses in the aetiology of MS.

Several lines of investigation have provided strong indications for an association between the immune-mediated, neurologic disease multiple sclerosis (MS) and human endogenous retroviruses (HERVs). Whether the relationship is causal is yet to be established. Endogenous retroviruses are pathogenic-in other species than the human. Several aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for cells in the periphery and in the central nervous system. Specific HERV-encoded genes and certain gene products (envelope proteins, Envs) appear strongly associated with the disease and have pathogenic potential. Most HERV sequences are non-functional, whereas some HERV loci have coding potential but remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, de-repression, and also involvement of retroviral restriction factors, is emerging. Disease intervention by means of antiretrovirals has potential as a novel therapeutic strategy in MS treatment; this is compounded by the apparently reduced risk of MS in HIV infection as a consequence of therapy. Extensive studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are needed.

Changes in the utilization of psychiatric hospital facilities in Denmark by patients diagnosed with schizophrenia from 1970 through 2012: The advent of 'revolving door' patients.

OBJECTIVE: The Danish psychiatric system has gone through several structural changes in the last four decades. The deinstitutionalization of the mental healthcare system was implemented in Denmark in the late 1970s with the intention of increasing out-patient treatment. One of the aims in the reorganization was to treat the patient in the local environment rather than during long-term hospitalization. This study focuses on the changes in the utilization of hospital facilities. METHOD: Using register data from secondary healthcare treatment of patients diagnosed with schizophrenia in Denmark 1970-2012, we analysed the development in the use of hospital facilities. RESULTS: Our major finding was a 220% increase between 1970 and 2012 in the total number of hospital admissions due to schizophrenia each year, while at the same time the number of annual schizophrenia bed days was reduced by 76%. Furthermore, the readmission rate within a year after discharge with a diagnosis of schizophrenia reached 70% in 2012 compared to 51% in 1970. Finally, the total bed occupancy continued to rise over the four decades and has exceeded 100% in several years since 1999. CONCLUSION: The findings indicate that the reorganization of the Danish mental healthcare system has created a problem of 'revolving door' schizophrenia patients' who since the 1970s have been increasingly hospitalized but for shorter periods. Possible explanations of the findings are premature discharge of patients with schizophrenia due to lack of beds or/and that community psychiatry has not been providing adequate relapse prevention.

Early warning score predicts acute mortality in stroke patients.

OBJECTIVES: Clinical deterioration and death among patients with acute stroke are often preceded by detrimental changes in physiological parameters. Systematic and effective tools to identify patients at risk of deterioration early enough to intervene are therefore needed. The aim of the study was to investigate whether the aggregate weighted track and trigger system early warning score (EWS) can be used as a simple observational tool to identify patients at risk and predict mortality in a population of patients with acute stroke. MATERIALS AND METHODS: Patients admitted with acute stroke at the Copenhagen University Hospital, Nordsjaellands Hospital, Denmark, from May to September 2012 were enrolled in a retrospective cohort study (n = 274). Vital signs were measured immediately after admission and consistently during the hospitalization period. Based on the vital signs, a single composite EWS was calculated. Death within 30 days was used as outcome. Area under the receiver operating characteristics curve (AUROC) and a Kaplan-Meier curve were computed to examine the prognostic validity of EWS. RESULTS: A total of 24 patients (8.8%) died within 30 days. The prognostic performance was high for both the EWS at admission (AUROC 0.856; 95% CI 0.760-0.951; P-value < 0.001) and the maximal EWS measured (AUROC 0.949; 95% CI 0.919-0.980; P-value < 0.001). Mortality rates were lowest for admission EWS 0-1 (2%) and highest for admission EWS ≥ 5 (63%). CONCLUSIONS: Early warning score is a simple and valid tool for identifying patients at risk of dying after acute stroke. Readily available physiological parameters are converted to a single score, which can guide both nurses and physicians in clinical decision making and resource allocation.

Second-generation antipsychotic effect on cognition in patients with schizophrenia--a meta-analysis of randomized clinical trials.

OBJECTIVE: To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. METHOD: Multiple-treatments meta-analysis model. RESULTS: On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12-1.63, quetiapine, ES 0.75; 95% CI: 0.00-1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14-1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00-0.74, olanzapine, ES 0.31; 95%CI: 0.02-0.59, quetiapine, ES 0.34; 95% CI: 0.03-0.64, and FGAs, ES 0.51; 95% CI: 0.18-0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04-0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06-1.58, olanzapine, ES 0.81; 95% CI: 0.07-1.55, quetiapine, ES 0.76; 95% CI: 0.02-1.51, ziprasidone, ES 0.90; 95% CI: 0.14-1.67, and FGAs, ES 0.83; 95% CI: 0.08-1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02-1.91, and quetiapine, ES 0.36; 95% CI: 0.01-0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06-0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01-0.50, and clozapine, ES 0.44; 95% CI: 0.06-0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04-0.78, and clozapine, ES 0.44; 95% CI: 0.05-0.83, performed poorer on visuospatial skill compared to olanzapine. CONCLUSION: The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.

Cost-effectiveness of insulin degludec compared with insulin glargine for patients with type 2 diabetes treated with basal insulin - from the UK health care cost perspective.

AIMS: The aim of this analysis was to evaluate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine (IGlar) in adults with type 2 diabetes mellitus (T2DM) who are considered appropriate for treatment with a basal insulin analogue, using a short-term economic model. METHODS: Meta-analysis data from three phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg versus IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. RESULTS: IDeg is a cost-effective treatment option versus IGlar in patients with T2DM using basal insulin. Base case incremental cost-effectiveness ratios (ICERs) were estimated at £15,795 per quality-adjusted life-year (QALY) and £13,078 per QALY, which are below commonly accepted thresholds for cost-effectiveness. Sensitivity analyses demonstrated that hypoglycaemia event rates had an important effect on the results. With higher event rates for non-severe hypoglycaemia IDeg was less costly and more effective than IGlar (dominant). Conversely, using lower event rates for severe hypoglycaemia generated higher ICERs. Using hypoglycaemia rates from a subgroup of patients who experienced ≥1 hypoglycaemic event per year IDeg was highly cost-effective versus IGlar; with estimated ICERS of £4887 and £2625 per QALY. CONCLUSIONS: This short-term modelling approach allows the economic evaluation of newer insulin analogues when advanced long-term modelling based on HbA1c differences is inappropriate. For patients with T2DM who are considered appropriate for treatment with a basal insulin analogue, IDeg is a cost-effective treatment option compared with IGlar and offers additional benefits to subgroups of patients, such as those suffering from recurrent hypoglycaemia.

Cognitive remediation combined with an early intervention service in first episode psychosis.

OBJECTIVE: This randomised clinical trial assessed the effects of a 16-week cognitive remediation programme (NEUROCOM) combined with an early intervention service (EIS) vs. EIS alone. METHOD: One hundred and seventeen patients with first episode psychosis were randomly assigned to 4 months cognitive remediation combined with EIS vs. EIS alone. Statistical analysis of effect was based on intention to treat. RESULTS: A total of 98 patients (83.8%) participated in post-training assessments at 4 months and 92 (78.6%) in 12-month follow-up assessments. No effects were found on the primary outcome measure functional capacity. At the post-training assessment, the intervention group had improved significantly on Rosenberg Self-Esteem Scale (Cohen's d=0.54, P=0.01), Positive and Negative Symptoms Scale (PANSS), General Psychopathology Scale (Cohen's d=0.51, P=0.05) and the verbal learning domain (Cohen's d=0.46, P=0.02). At follow-up assessment, the intervention group retained the significant improvements on the verbal learning domain (Cohen's d=0.58, P<0.05). Furthermore, significant improvements were observed on the working memory domain (Cohen's d=0.56, P=0.01) and PANSS positive symptoms (Cohen's d=0.44, P=0.04), while improvement on the composite score was marginally significant (Cohen's d=0.34, P=0.05). CONCLUSION: In accordance with other cognitive remediation programmes, this programme demonstrates some immediate and long-term effect on cognitive functioning, symptoms and self-esteem.

Effectiveness of offering healthy labelled meals in improving the nutritional quality of lunch meals eaten in a worksite canteen.

Healthier meal selections at restaurants and canteens are often limited and not actively promoted. In this Danish study the effectiveness of a healthy labelling certification program in improving dietary intake and influencing edible plate waste was evaluated in a quasi-experimental study design. Employees from an intervention worksite canteen and a matched control canteen were included in the study at baseline (February 2012), after completing the certification process (end-point) and six month from end-point (follow-up) (total n=270). In order to estimate nutrient composition of the consumed lunch meals and plate waste a validated digital photographic method was used combining estimation of food intake with food nutrient composition data. Food satisfaction was rated by participants using a questionnaire. Several significant positive nutritional effects were observed at the intervention canteen including a mean decrease in energy density in the consumed meals from 561kJ/100g at baseline to 368 and 407kJ/100g at end-point and follow-up, respectively (P<0.001). No significant changes were seen with regard to food satisfaction and plate waste. In the control canteen no positive nutritional effects were observed. The results of the study highlight the potential of using healthy labelling certification programs as a possible driver for increasing both the availability and awareness of healthy meal choices, thereby improving dietary intake when eating out.

WebDASC: a web-based dietary assessment software for 8-11-year-old Danish children.

BACKGROUND: The present study describes the development and formative evaluation of the Web-based Dietary Assessment Software for Children (WebDASC). WebDASC is part of the OPUS project ('Optimal well-being, development and health for Danish children through a healthy New Nordic Diet') and was intended to measure dietary change resulting from a school-based intervention. METHODS: WebDASC was developed as a self-administered tool that could be used by 8-11-year-old children with or without parent's aid. The development of WebDASC followed a prototyping approach: focus groups, informal interviews, literature review, and usability tests preceded its release. Special consideration was given to age-appropriate design issues. RESULTS: In WebDASC an animated armadillo guides respondents through six daily eating occasions and helps them report foods and beverages previously consumed. A database of 1300 food items is available either through category browse or free text search, aided by a spell check application. A type-in format is available for foods not otherwise found through category browse or text search. Amount consumed is estimated by selecting the closest portion size among four different digital images. WebDASC includes internal checks for frequently forgotten foods, and the following features to create motivation: a food-meter displaying cumulative weight of foods reported, a most popular food ranking, and a computer game with a high score list. CONCLUSIONS: WebDASC was developed as an intuitive, cost-effective, and engaging method to collect detailed dietary data from 8- to 11-year-old children. Preliminary testing demonstrated that it was well accepted among children.

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease.

BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4µg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary. CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.

Why is welfare pork so expensive?

Specialty (niche) pork products may provide societal benefits in terms of e.g. higher animal welfare, reduced use of antibiotics, and lower environmental impact. At the same time, they offer a business opportunity for farmers, slaughterhouses, meat processers, and retailers, who can capitalise on consumer segments willing to pay a price premium. However, the added cost of delivering niche products and a limited willingness among consumers to pay the higher prices may negate the benefits of this approach, particularly as niche products typically have high substitutability with standard pork. One way to ensure the success of the niche pork products is to drive down costs across all parts of the value chain. Inspired by data from the Danish pork market, the present study seeks to identify cost drivers in the value chain. We found two promising approaches to reduce the costs associated with niche products. First, the pricing strategy can be altered so that mainstream pork is replaced entirely by specialty pork products in the chiller section, thereby making niche the new standard. Second, with improved carcass balance, the price premium paid to farmers can be assigned to a larger proportion of the pig, thus enabling the retail price to be lowered. For example, we found that improved carcass balance had the potential to halve the necessary retail price increase, regardless of the pricing strategy employed. The conclusion is that it is possible to drive down costs across all parts of the value chain to enable further production and profitable sale of welfare pork.

Waste LCA and the future.

Life cycle assessment (LCA) models quantifying the environmental aspects of waste management have become an integral part of waste management decision-making over the last two decades and have provided ample knowledge on both environmental benefits and drawbacks in the way we handle waste. Waste management and LCA modelling of waste management systems will soon be challenged by profound changes necessary in our societies and sectors to meet sustainable development goals. Foreseen changes in energy, material, and nutrient provision will directly and indirectly affect waste management in terms of its operation and goals. This study reflects on anticipated changes in society and industrial sectors and how these changes may affect waste management and LCA modelling of waste management systems in terms of waste input, the modelling of technologies and systems and exchanges of energy, materials, and nutrients, as well as how it may affect impact assessment and the interpretation of results. The study provides practical recommendations for LCA modelling of future waste management systems, which will hopefully lead to robust assessments that can support decision-making in an evolving society subject to great changes.

Circulating immune-related proteins associated with immune checkpoint inhibitor efficacy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint inhibitor treatment. However, the phase II study CheckPAC (NCT02866383) showed a clinical benefit (CB) rate of 37% and a response rate of 14% in patients with metastatic PDAC receiving stereotactic radiation therapy and nivolumab with or without ipilimumab. Translational studies were initiated to characterize the patients who would benefit from this treatment. Here, we evaluated the association between treatment outcome and 92 circulating immuno-oncology-related proteins in patients from the CheckPAC trial. MATERIALS AND METHODS: The study included 78 patients with chemoresistant metastatic PDAC treated with nivolumab ± ipilimumab combined with radiotherapy. Proteins were measured in serum samples collected at baseline and on treatment with the use of the Olink Target 96 Immuno-Oncology panel. A cohort of 234 patients with metastatic PDAC treated with first-line chemotherapy were also included. RESULTS: High levels of Fas ligand (FASLG) and galectin 1 (Gal-1) and low levels of C-C motif chemokine 4 were associated with CB. High FASLG and Gal-1 were associated with longer progression-free survival in univariable analysis. In the multivariable Cox regression analysis, the association was significant for Gal-1 (P < 0.001) but not significant for FASLG (P = 0.06). A focused unsupervised hierarchal clustering analysis, including T-cell activation and immune checkpoint-related proteins, identified clusters of patients with higher CB rate and higher tumor expression of leukocyte or T-cell markers (CD3, CD45, granzyme B). Thirty-six proteins increased significantly during immunotherapy. Several proteins (including FASLG, checkpoint proteins, and immune activation markers) increased independently of response during immunotherapy but did not increase in the cohort of patients treated with chemotherapy. CONCLUSIONS: Circulating levels of immune-related proteins like FASLG and Gal-1 might be used to predict the efficacy of checkpoint inhibitors in patients with metastatic PDAC.

Flow cytometric assay detecting cytotoxicity against human endogenous retrovirus antigens expressed on cultured multiple sclerosis cells.

Damage of target cells by cytotoxicity, either mediated by specific lymphocytes or via antibody-dependent reactions, may play a decisive role in causing the central nervous system (CNS) lesions seen in multiple sclerosis (MS). Relevant epitopes, antibodies towards these epitopes and a reliable assay are all mandatory parts in detection and evaluation of the pertinence of such cytotoxicity reactions. We have adapted a flow cytometry assay detecting CD107a expression on the surface of cytotoxic effector cells to be applicable for analyses of the effect on target cells from MS patients expressing increased amounts of human endogenous retrovirus antigens. MS patients also have increased antibody levels to these antigens. The target cells are spontaneously growing peripheral blood mononuclear cells (PBMCs) of B cell lineage, expressing human endogenous retrovirus HERV epitopes on their surface. Polyclonal antibodies against defined peptides in the Env- and Gag-regions of the HERVs were raised in rabbits and used in antibody-dependent cell-mediated cytotoxicity (ADCC) -assays. Rituximab® (Roche), a chimeric monoclonal antibody against CD20 expressed primarily on B cells, was used as control antibody. Without antibodies this system is suitable for analyses of natural killer cell activity. In optimization of the assay we have used effector lymphocytes from healthy donors. The most effective effector cells are CD56(+) cells. CD8(+) T cells also express CD107a in ADCC. Using the adapted assay, we demonstrate significant ADCC activity to target cells expressing HERV epitopes, and additionally a low level of NK activity.

Insulin degludec improves health-related quality of life (SF-36® ) compared with insulin glargine in people with Type 2 diabetes starting on basal insulin: a meta-analysis of phase 3a trials.

AIM: To compare the effect of insulin degludec and insulin glargine on health-related quality of life in patients with Type 2 diabetes starting on insulin therapy. METHODS: Patient-level data from three open-label, randomized, treat-to-target trials of 26 or 52 weeks' duration were pooled using a weighted analysis in conjunction with a fixed-effects model. Insulin-naive patients received either insulin degludec (n = 1290) or insulin glargine (n = 632) once daily, in combination with oral anti-diabetic drugs. Glycaemic control was assessed via HbA(1c) and fasting plasma glucose concentrations. Rates of hypoglycaemia, defined as plasma glucose < 3.1 mmol/l (< 56 mg/dl), were recorded. Health-related quality of life was evaluated using the 36-item Short Form (SF-36(®) ) version 2 questionnaire. Statistical analysis was performed using a generalized linear model with treatment, trial, anti-diabetic therapy at baseline, gender, region and age as explanatory variables. RESULTS: Insulin degludec was confirmed as non-inferior to insulin glargine based on HbA(1c) concentrations. In each trial comprising the meta-analysis, fasting plasma glucose and confirmed overall and nocturnal (00.01-05.59 h) hypoglycaemia were all numerically or significantly lower with insulin degludec vs. insulin glargine. At endpoint, the overall physical health component score was significantly higher (better) with insulin degludec vs. insulin glargine [+0.66 (95% CI 0.04-1.28)], largely attributable to a difference [+1.10 (95% CI 0.22-1.98)] in the bodily pain domain score. In the mental domains, vitality was significantly higher with insulin degludec vs. insulin glargine [+0.81 (95% CI 0.01-1.59)]. CONCLUSIONS: Compared with insulin glargine, insulin degludec leads to improvements in both mental and physical health status for patients with Type 2 diabetes initiating insulin therapy.

A nine country study of the burden of non-severe nocturnal hypoglycaemic events on diabetes management and daily function.

AIMS: The purpose of this study was to explore the burden and impact of non-severe nocturnal hypoglycaemic events (NSNHEs) on diabetes management, patient functioning and well-being in order to better understand the role that NSNHEs play in caring for persons with diabetes and facilitate optimal diabetes treatment management strategies. METHODS: A 20-min survey assessing the impact of NSNHEs was administered to patients with self-reported diabetes age 18 or older via the Internet in nine countries (USA, UK, Germany, Canada, France, Italy, Spain, The Netherlands and Sweden) who experienced an NSNHE in the last month. Questions captured reasons for and length of the event, and impacts on diabetes management, daily function, sleep and well-being. RESULTS: A total of 20 212 persons with Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) were screened of which 2108 respondents were eligible. Respondents initiated, on average, an additional 3.6 glucose monitoring tests, and did not resume usual functioning for an average of 3.4 hours after the NSNHE. Of the respondents using insulin, 15.8% decreased their insulin dose over an average of 3.6 days. NSNHEs also impacted sleep, with 10.4% not returning to sleep that night. Next day functioning was affected with 60.3% (n = 1273) feeling the need to take a nap and/or rest (with 65.5% of those actually taking a nap/rest) and 40.2% (n = 848) wanting to go to bed earlier than usual. A total of 21.4% were restricted in their driving the next day. These events also resulted in decreased well-being with 39.6% of respondents feeling 'emotional low' the following day. CONCLUSIONS: NSNHEs have serious consequences for patients. Greater attention to patient and physician education regarding the burden of NSNHEs and incorporation of corrective actions in treatment plans is needed to facilitate patients reaching optimal glycaemic control.

A comparison of health-related quality of life (health utility) between insulin degludec and insulin glargine: a meta-analysis of phase 3 trials.

AIM: To evaluate health-related quality of life (health utility) scores in patients with diabetes receiving insulin degludec (IDeg) or insulin glargine (IGlar). METHODS: Patient-level data from six, randomized, controlled, open-label, multicentre, confirmatory, treat-to-target trials of 26- or 52 weeks' duration were pooled in this analysis. The Short Form 36 (SF-36) version-2 health questionnaire was completed by patients at baseline and end-of-trial. SF-36 scores for 4001 individual patients were then mapped onto the EuroQol-5D health utility scale, which has a range from -0.59 (a state worse than death) to 1.00 (perfect health). RESULTS: IDeg treatment exhibited a significant improvement in health status of 0.005 (CI: 0.0006; 0.009) points compared with IGlar (p < 0.024). Gender, region, trial and age also had a significant influence on estimated utility scores as did baseline utility scores, p < 0.05. Prior to the removal of interaction variables a difference of 0.008 points was observed, p < 0.045. Previous insulin treatment did not have an impact on the final outcome. CONCLUSION: This study shows that IDeg is associated with a modest, but statistically significant, improvement in health utility compared with IGlar in patients with diabetes.